TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17739	53440;53441;53442	chr2:178607473;178607472;178607471	chr2:179472200;179472199;179472198
N2AB	16098	48517;48518;48519	chr2:178607473;178607472;178607471	chr2:179472200;179472199;179472198
N2A	15171	45736;45737;45738	chr2:178607473;178607472;178607471	chr2:179472200;179472199;179472198
N2B	8674	26245;26246;26247	chr2:178607473;178607472;178607471	chr2:179472200;179472199;179472198
Novex-1	8799	26620;26621;26622	chr2:178607473;178607472;178607471	chr2:179472200;179472199;179472198
Novex-2	8866	26821;26822;26823	chr2:178607473;178607472;178607471	chr2:179472200;179472199;179472198
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-113
• Domain position: 63
• Structural Position: 151
• Q(SASA): 0.5312
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
H/L	None	None	0.959	N	0.515	0.294	0.663800828988	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
H/N	rs1419607621	0.145	0.959	N	0.478	0.297	0.280181792013	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
H/N	rs1419607621	0.145	0.959	N	0.478	0.297	0.280181792013	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/N	rs1419607621	0.145	0.959	N	0.478	0.297	0.280181792013	gnomAD-4.0.0	7.69235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43707E-05	0	0
H/R	rs1488100561	None	0.979	N	0.533	0.325	0.281780670237	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/R	rs1488100561	None	0.979	N	0.533	0.325	0.281780670237	gnomAD-4.0.0	6.57722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47171E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
H/A	0.4367	ambiguous	0.6326	pathogenic	-0.353	Destabilizing	0.864	D	0.363	neutral	None	None	None	None	N
H/C	0.2485	likely_benign	0.3624	ambiguous	0.567	Stabilizing	0.039	N	0.346	neutral	None	None	None	None	N
H/D	0.5016	ambiguous	0.714	pathogenic	-0.158	Destabilizing	0.959	D	0.528	neutral	N	0.435548853	None	None	N
H/E	0.5677	likely_pathogenic	0.7741	pathogenic	-0.095	Destabilizing	0.969	D	0.477	neutral	None	None	None	None	N
H/F	0.5133	ambiguous	0.6571	pathogenic	0.486	Stabilizing	0.999	D	0.612	neutral	None	None	None	None	N
H/G	0.4405	ambiguous	0.5817	pathogenic	-0.688	Destabilizing	0.927	D	0.473	neutral	None	None	None	None	N
H/I	0.7048	likely_pathogenic	0.8773	pathogenic	0.548	Stabilizing	0.995	D	0.554	neutral	None	None	None	None	N
H/K	0.4525	ambiguous	0.6685	pathogenic	-0.183	Destabilizing	0.969	D	0.533	neutral	None	None	None	None	N
H/L	0.356	ambiguous	0.5688	pathogenic	0.548	Stabilizing	0.959	D	0.515	neutral	N	0.50125377	None	None	N
H/M	0.6671	likely_pathogenic	0.8198	pathogenic	0.489	Stabilizing	0.999	D	0.499	neutral	None	None	None	None	N
H/N	0.1901	likely_benign	0.3405	ambiguous	-0.019	Destabilizing	0.959	D	0.478	neutral	N	0.454307972	None	None	N
H/P	0.7372	likely_pathogenic	0.8607	pathogenic	0.27	Stabilizing	0.994	D	0.565	neutral	N	0.49378908	None	None	N
H/Q	0.3346	likely_benign	0.5357	ambiguous	0.16	Stabilizing	0.994	D	0.568	neutral	N	0.445611131	None	None	N
H/R	0.2276	likely_benign	0.3943	ambiguous	-0.746	Destabilizing	0.979	D	0.533	neutral	N	0.431143111	None	None	N
H/S	0.2951	likely_benign	0.4442	ambiguous	-0.007	Destabilizing	0.546	D	0.211	neutral	None	None	None	None	N
H/T	0.3696	ambiguous	0.5735	pathogenic	0.147	Stabilizing	0.939	D	0.511	neutral	None	None	None	None	N
H/V	0.5905	likely_pathogenic	0.8032	pathogenic	0.27	Stabilizing	0.969	D	0.532	neutral	None	None	None	None	N
H/W	0.576	likely_pathogenic	0.7199	pathogenic	0.59	Stabilizing	1.0	D	0.487	neutral	None	None	None	None	N
H/Y	0.2035	likely_benign	0.3309	benign	0.831	Stabilizing	0.993	D	0.489	neutral	N	0.493962438	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.